Tumor Treating Fields Therapy After Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer: Final Results of the Phase 3 METIS Study
Bibliographic record
Abstract
PURPOSE: Improved treatments for brain metastases from non-small cell lung cancer (NSCLC BM) are needed to prolong time to intracranial progression (TTIP) without increasing neurotoxicity. Tumor Treating Fields (TTFields), electric fields delivered via skin-based arrays that disrupt cancer cell division, have demonstrated efficacy and safety in glioblastoma, NSCLC, and pancreatic cancer. METHODS AND MATERIALS: In the phase 3 METIS trial (NCT02831959), adults with 1 to 10 newly diagnosed NSCLC BMs suitable for stereotactic radiosurgery (SRS) receiving optimal therapy for extracranial disease were randomized 1:1 to SRS followed by TTFields (150 kHz) or SRS alone. Radiologic progression was assessed by an independent radiology review committee. The primary endpoint was TTIP (Response Assessment in Neuro-Oncology Brain Metastases criteria). Secondary endpoints included overall survival, neurocognitive function, quality of life (QoL), and safety. RESULTS: Patients (N = 298) were followed for a median of 8.6 (0.07-85.2) months. TTFields significantly delayed TTIP (hazard ratio [HR], 0.72 [95% CI, 0.53-0.98]; Fine-Gray P = .044). Intracranial progression rates at months 2, 6, 12, and 24 were 13.6% versus 22.1% (P = .034), 33.7% versus 46.4% (P = .018), 46.9% versus 59.4% (P = .023), and 53.6% versus 65.2% (P = .031; post hoc). Time to distant intracranial progression favored TTFields therapy, although not statistically significantly (HR, 0.76 [95% CI, 0.51-1.12]; log-rank P = .165; post hoc). In patients receiving immune checkpoint inhibitors (n = 118), the delays in both TTIP (HR, 0.63 [95% CI, 0.39-1.0]; Cox P = .049; Fine-Gray P = .055) and time to distant intracranial progression (HR, 0.41 [95% CI, 0.21-0.81]; log-rank P = .0087, post hoc) were more pronounced. Device-related adverse events were mainly grade ≤2 skin events. TTFields did not cause QoL deterioration, and improvements in deterioration-free survival and time to deterioration of the global health status, physical functioning and fatigue domains were observed (post hoc). CONCLUSIONS: By significantly prolonging TTIP, without worsening QoL or cognitive function, TTFields after SRS is a new treatment option for patients with NSCLC BMs, including those receiving immune checkpoint inhibitor.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".